FORM 2
PATENT ACT 1970
(39 OF 1970)
&
PATENT RULE 2003
(See Section 10 & Rule 13)
(COMPLETE SPECIFICATION)
TITLE OF THE INVENTION - "A synergistic combined Pharmaceutical composition of an active antipyretic and analgesic and administrations thereof.
NAME OF APPLICANT- Zota Health Care Limited
ADDRESS OF APPLICANT- Zota Health Care Limited
ZOTA HOUSE
2/896, HDRA MODI STREET,
SAGRAMPURA,
SURAT-395 002. (GUJARAT).
INDIA.
PREAMBLE OF INVENTION- This invention in particular describes the nature of the invention and the manner in which it is to be performed.

FIELD OF THE INVENTION
The present invention relates to a stable, cost effective and time saving pharmaceutical composition, which comprises an antipyretic and analgesic paracetamol with optimum bioavailability and desirable properties.
BACKGROUND OF THE INVENTION
Acetaminophen, also known as paracetamol, is commonly used for its analgesic and antipyretic effects. Its therapeutic effects are similar to salicylates, but it lacks anti-inflammatory, antiplatelet, and gastric ulcerative effects.
Paracetamol has been in use as an analgesic for home medication for over 30 years and is accepted as a very effective treatment for the relief of pain and fever in adults and children. In 1893, paracetamol, was noted also to have a prompt analgesic and antipyretic action. In 1895, further work on this compound indicated that paracetamol might be present in the urine of patients who had taken phenacetin and in 1889, paracetamol was also shown to be a urinary metabolite of acetanilide.
According to WO 2009/118764 Al (patent application)/IN2009/000201 (Indian patent application) wherein Compositions comprising a combination of diclofenac and paracetamol, or pharmaceutically acceptable salts, esters, polymorphs, isomers, prodrugs, solvates, hydrates, or derivatives thereof as active agents, optionally in association with one or more pharmaceutically acceptable excipient(s) are provided whereby paracetamol and diclofenac are present in the combination in such amounts that the effect of the composition is more favorable than the added effects of the amounts of each drug separately. The present invention also provides process of preparing such compositions and methods of using them. The composition of the present invention are safe, effective and well-tolerated, and are useful for the management such as prophylaxis, amelioration andVor treatment of pain associated with or without inflammation and/or other associated disease(s)/disorder(s).
According to European Patent EP1465663 wherein said The present invention refers to ready-to-use highly stable paracetamol combination solutions, prepared by mixing paracetamol, water,

propylene glycol, and a citrate buffer. (pH 4.5 to 6.5), and by heating said solution under preset conditions. The resulting solution may be stored for an extended period of time within a wide range of temperatures, with no paracetamol precipitation and/or its chemical modification.
According to 1746/MUM/2008 A wherein said The present invention refers to a pharmaceutical formulation for paracetamol injection which comprises paracetamol, glycofurol, co-solvent, water and preservative. This formulation provides ease of administration to the patient, less pain to the patient and high effectiveness. The said formulation is ready to use formulation so no dilution is required at the time of injecting solution. The said formulation is available in 2 ml, 3 ml and 5 ml.
According to United States Patent 6423749 wherein said the invention relates to pharmaceutical compositions comprising paracetamol, ethanol, and polyethylene glycol, either in the absence or the presence of water.
According to United States Patent: 6,028,222 wherein said Novel stable paracetamol compositions for use in therapeutic chemistry and specifically galenic pharmacy are disclosed. The compositions contain a solution of paracetamol in an aqueous solvent combined with a buffer having a pH of 4 to 8, and a free radical capturing agent. A water-insoluble inert gas is carefully bubbled through the aqueous solvent to remove oxygen from the medium. Said compositions may also be combined with a centrally or peripherally acting analgesic agent, and are provided as injectable compositions for relieving pain
According to EP1285667 (Bl) wherein said These solutions comprise as active Ingredient or ingredients Paracetamol and combinations of Paracetamol with the spasmolytic HYOSCINE-N-BUTYLBROMIDE and the analgesic CODEINE PHOSPHATE where the solvent in all cases consists of Ethanol, bis-distilled and sterilized Water and GLYCEROL FORMAL or Benzyllic Alcohol, Water and GLYCEROL FORMAL in the ratio of 10, 40 kappa alpha 50% by volume. The solution is also comprised of LIDOCAINE as local anaesthetic and DISODIUM EDETATE , SODIUM METABISULFITE, SODIUM DIBASIC PHOSPHATE, NIPAGIN A and NIPASOL M, excipients assuring solutions stability and maintenance of pH in the desired limits of 5,0 - 6,5.

SUMMARY OF THE INVENTION
In general, the invention relates to pharmaceutical composition comprising an active antipyretic and analgesic ("Compound 1"). The pharmaceutical compositions may also include one or more of the following excipients: solvent, solubilizer and a surfactant thereof.
In one embodiment, the present invention provides a combination pharmaceutical composition comprising an active antipyretic and analgesic Compound paracetamol, wherein the composition comprises various amount.
Another object of the invention is suitable for those peoples who are sensitive to aspirin.
The object of the invention provides an effective combination formulation is suitable for children, and can be given to babies to treat the raised temperature that may follow immunisation.
Another object of the invention provides a highly effective and lack of side-effects contained combination pharmaceutical composition that contains active analgesic and antipyretic compound with others.
Another object of the invention provides relief to some asthma sufferers who have a sensitivity to aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs e.g. ibuprofen)
Another object of the invention preferred analgesic contained combination for asthma sufferers, because aspirin and ibuprofen are much more likely to precipitate asthma attacks and are to be avoided by asthma sufferers.
Another object of the invention provides active ingredient Paracetamol who has no blocking action and can be used for pain relief without affecting the protective effects of low dose aspirin or other NSAIDS used in the prevention of heart disease and stroke.

DETAILED DESCRIPTION OF THE INVENTION
This invention relates to pharmaceutical composition which comprises active pharmaceutical ingredient with other ingredients for example glycofurol, hydroxylpropylbeta dextrin thereof.
As used herein, the term "active pharmaceutical ingredient" or "API" refers to a biologically active compound. Exemplary APIs include Paracetamol
As used herein, an "excipient" is an inactive ingredient in a pharmaceutical composition. Examples of excipients include fillers or diluents, surfactants, glidants, lubricants, disintegrants, and the like.
As used herein, the term "pharmaceutically acceptable salt" refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. A "pharmaceutically acceptable salt" means any non-toxic salt or salt of an ester of a compound of this invention.
This composition is used for the relief of fever, headaches, and other minor aches and pains. It is a major ingredient in numerous cold and flu medications and many prescription analgesics. It is extremely safe in standard composition, but because of its wide availability, deliberate or accidental overdoses are not uncommon. Paracetamol unlike other common analgesics such as aspirin and ibuprofen, has no anti-inflammatory properties or effects on platelet function, and it is not a member of the class of drugs known as non-steroidal anti-inflammatory drugs or NSAIDs. At therapeutic doses paracetamol does not irritate the lining of the stomach nor affect blood coagulation, kidney function, or the fetal ductus arteriosus (as NSAIDs can). Like NSAIDs and unlike opioid analgesics, paracetamol does not cause euphoria or alter mood in any way. Paracetamol and NSAIDs have the benefit of being completely free of problems with addiction, dependence, tolerance and withdrawal. Paracetamol is used on its own or in combination with pseudoephedrine, dextromethorphan, chlorpheniramine, diphenhydramine, doxylamine, codeine, hydrocodone, or oxycodone.

The Mechanism of action
Paracetamol is thought to act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin (PG) synthesis. Unlike NSAIDs, paracetamol does not inhibit cyclooxygenase in peripheral tissues and, thus, has no peripheral anti-inflammatory affects. While aspirin acts as an irreversible inhibitor of COX and directly blocks the enzyme's active site, studies have found that paracetamol indirectly blocks COX, and that this blockade is ineffective in the presence of peroxides. This might explain why paracetamol is effective in the central nervous system and in endothelial cells but not in platelets and immune cells which have high levels of peroxides. Studies also report data suggesting that paracetamol selectively blocks a variant of the COX enzyme that is different from the known variants COX-1 and COX-2. This enzyme is now referred to as COX-3. Its exact mechanism of action is still poorly understood, but future research may provide further insight into how it works. The antipyretic properties of paracetamol are likely due to direct effects on the heat-regulating centres of the hypothalamus resulting in peripheral vasodilation, sweating and hence heat dissipation. Its analgesic (pain relief) and antipyretic (fever relief) effects are comparable to those of aspirin.
• There are virtually no groups of people who should not take it.
• Interactions with other treatments are not a problem.
• At the recommended dosage there are virtually no side-effects.
• It is well tolerated by patients with peptic ulcers.
This composition relieves pain and fever in adults and children, and it is the most widely accepted medicine for this purpose.
Another embodiment of the invention is Glycofurol who does not cause irritation when applied as
a dilute solution. Toxicity Profiles are comprehensive, yet concise, monographs on the hazard
potential of individual chemicals. It may available in Parenteral, Oral form, inhaler and nebulizer
thereof.
When taken at the recommended dosage, there are virtually no side-effects.
This pharmaceutical composition can be combined with decongestant ingredients to help relieve

the symptoms of the common cold, influenza and sinusitis by relieving headache, general aches,
nasal congestion and fever thereof.
This combination is suitable for immediate consumption or for dissolving in water before
consumption. It is suitable for all age groups including the very young for whom it may be used
following immunisation procedures.
The pharmaceutical compositions of the present invention can be processed into a
Another aspect of the present invention provides a pharmaceutical active ingredient
Hydroxypropyl Beta Cyclodextrin wherein p-Cyclodextrin is a new stuff which can be widely
applied in production of whose function is improved stability, solubility and good smelled. In the
production of medicine, it can strengthen the stability of medicine without being oxidized and
resolving. On the other hand, it can improve the solubility. And the effect on living of medicine,
lower the toxic and side-effect of medicine and cover the strange and bad smell.
In the present invention, Hydroxypropyl B-Cyclodextrin Endotoxin is used as being suitable for
pharmaceutical use. It is a water soluble, free flowing, white odourless powder., In addition to
increase the solubility, the stability of the paracetamol compound can be enhanced and the
volatility can be reduced. Hydroxypropyl B-Cyclodextrin Endotoxin is chemically stable and does
not contribute significantly to viscosity until very high concentrations. It is non- mutagenic. The
main advantage of Hydroxypropyl B-Cyclodextrin Endotoxin (HPBCD) is the increased solubility
of the complexes. HPBCD is used for solubilization and stabilization of paracetamol by
complexing with HPBCD, the paracetamol interacts with cavity of the HPBCD to become
entrapped. The outer surface of the HPBCD is very hydrophilic and interacts well with water to
carry the paracetamol into solution. It can easily increase the permeability of paracetamol.
The main major Advantages of the invention is following
- It's Easy and very convenient way for ready administration -This combination has better bio-availability rate.
- This combination has highly stability.
- In the efficacy point of view it has Better efficacy.
- Due to above reasons it has Better tolerability.

CLAIMS. We claim,
1. A synergistic combined Pharmaceutical composition comprises of an active antipyretic and analgesic which is paracetamol and other pharmaceutical excipeients for example glycofurol, hydroxylpropylbetadextrin thereof.
2. A synergistic combined Pharmaceutical composition is claimed as claim 1 wherein said it provides a pharmaceutical composition comprising an active antipyretic and analgesic Compound 1, wherein the composition comprises in various concentration.
3. A synergistic combined Pharmaceutical composition is claimed as claim 1 wherein said Hydroxypropyl B-Cyclodextrin Endotoxin (HPBCD) is the increased solubility of the complexes. HPBCD is used for solubilization and stabilization of paracetamol by complexing with HPBCD, the paracetamol interacts with cavity of the HPBCD to become entrapped. The outer surface of the HPBCD is very hydrophilic and interacts well with water to carry the paracetamol into solution. It can easily increase the permeability of paracetamol.
4. A synergistic combined pharmaceutical composition is claimed as claim 1 wherein said Glycofurol does not cause irritation when applied as a dilute solution. Toxicity Profiles are comprehensive, yet concise, monographs on the hazard potential of individual chemicals..
5. A synergistic combined Pharmaceutical composition is claimed as claim 1 wherein said it provides a novel combination as a liquid pharmaceutical formulation of paracetamol that is stable for a prolonged period without having the drawbacks.
6. A synergistic combined Pharmaceutical composition is claimed as claim 1 wherein said it act as an antioxidant and makes it possible to dispense with the strong or toxic antioxidants described for the prior-art stabilized solutions of paracetamol.

7. A synergistic combined Pharmaceutical composition is claimed as claim 1 wherein said the formulation of the invention has excellent stability at room temperature
8. A synergistic combined Pharmaceutical composition is claimed as claim 1 wherein said when taken at the recommended dosage, there are virtually no side-effects.
9. A synergistic combined Pharmaceutical composition is claimed as claim 1 wherein said this combination is suitable for immediate consumption or for dissolving in water before consumption. It is suitable for all age groups including the very young for whom it may be used following immunization procedures.
10. A synergistic combined Pharmaceutical composition is claimed as claim 1 wherein said the pharmaceutical compositions of the present invention can be processed into Parenteral and oral form, inhaler, nebulizer thereof.